O-to-S acyl transfer

Speculate that an a,a-substituted variant might be an even better O-to-S acyl transfer reagent, and indeed, the calculated energy barrier of the O-to-S acyl transfer of a variant of (34) with an a-methyl group (37) was about 12kcal mol lower than the hydrolysis... 

Peptide thioester preparation via intramolecular O-to-S acyl transfer through Fmoc chemistry has been studied by computational chemistry and found to occur via an anionic stepwise mechanism in which the cleavage of the C-O bond is the rate-limiting... 

In the above aminolysis reactions, Mg2+ ion always activates P—O fission. Other divalent metal ions behave similarly. Change of nucleophile might result in the change of P—O to S—O fission. To pursue the possibility of metal ion catalyzed S—O fission under neutral conditions, we examined the catalysis of the Zn2+-pyridine-2-carboxaldoxime (Zn2+PCA) complex, since catalytic activity of this complex has been well known in some acyl and phosphoryl transfer reactions (18, 19, 20). However, the results described below again indicate that the complex promotes an exclusive P-O bond fission (21). 

As shown, under the reducing ligation conditions, 0—>S acyl transfer occurred at the o-disulfide phenolic ester as previously described (see above), to provide the thioester, which underwent transthioesteriflcation with the thiol-containing glyco-peptide (upon in situ reduction of the auxiliary disulfide bond) the transient intermediate underwent an S N acyl transfer to generate the thermodynamically favored amide bond of the doubly glycosylated peptide adduct. The auxiliary was subsequently removed through sequential methylation of the fi-ee thiol to prevent the reverse acid-mediated N S acyl shift, followed by TFA treatment. 

NCL has been achieved at unprotected Ser and Thr residues via an 0- to A-acyl transfer [81]. Hojo et al. employed a slightly different strategy in which a mercaptomethyl group was used to protect the Ser and Thr residues. In this instance the ligation step occurs through an S- to A-acyl transfer via a seven-membered ring and this approach was used to access O-linked glycoprotein contulakin-G (Fig. 20) [132]. 

We were also able to use FAB mass spectrometry to determine the amino acid sequence around the active site serine in the acyl transference domain of rabbit mammary fatty acid synthase.6 The synthase was labelled in the acyl transferase domain(s) by the formation of O-ester intermediates after incubation with [" " C]-acetyl- or malonyl-CoA (Fig. 2A). The modified protein was then digested with elastase (Fig. 2B), and radioactive material isolated via successive purification steps on Sephadex G-50 and reverse phase HPLC. The isolated peptides were then sequenced by FAB MS. The data summarized in Table II established the sequences of both the acetyl and malonyl hexapeptides to be N-acyl-Ser-leu-Gly-Glu-Val-Ala. 

Better for the lateral lithiation of phenols are the N,N-dialkylcarbamate derivatives 444. These may be lithiated with LDA, allowing complete selectivity for the lateral position, presumably because this is the thermodynamic product.192 With s-BuLi ortholithiation is the predominant reaction pathway. If the lateral organolithium 445 is warmed to room temperature, an acyl transfer from O to C takes place, analogous to the anionic ortho-Fries (see section 2.3.2.1.4), giving amide 446.365... 

Macrolides. Reaction of a-alkenyl cyclic sulfide (1) with dichloroketene is accompanied by a [3.3] sigmatropic rearrangement lo give the 10-membered thiolactone (2) (c/. 9, 153-154). After dechlorination and deprotection, reaction with camphorsulfonic acid (CSA) effects an S-to-O acyl transfer to give the mercapto lactone (3). 

Vedejs and Powell employed an acid-catalyzed intramolecular S to O acyl transfer process to convert the thionan-2-one (145) to the 10-membered lactone (146) in their synthesis of phor-acantholide I the nine-membered lactone (147) was formed under similar conditions from (148) (Scheme 12) <82JA2046>. 

An enzyme reaction intermediate (Enz—O—C(0)R or Enz—S—C(O)R), formed by a carboxyl group transfer (e.g., from a peptide bond or ester) to a hydroxyl or thiol group of an active-site amino acyl residue of the enzyme. Such intermediates are formed in reactions catalyzed by serine proteases transglutaminase, and formylglyci-namide ribonucleotide amidotransferase . Acyl-enzyme intermediates often can be isolated at low temperatures, low pH, or a combination of both. For acyl-seryl derivatives, deacylation at a pH value of 2 is about 10 -fold slower than at the optimal pH. A primary isotope effect can frequently be observed with a C-labeled substrate. If an amide substrate is used, it is possible that a secondary isotope effect may be observed as welF. See also Active Site Titration Serpins (Inhibitory Mechanism)... 

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